Nanoneedles for targeted siRNA silencing of p16 in the Human Corneal Endothelium

Nanoneedles can target nucleic acid transfection to primary cells at tissue interfaces with high efficiency and minimal perturbation. The corneal endothelium is an ideal target for nanoneedle-mediated RNAi aimed at enhancing its proliferative capacity, necessary for tissue regeneration. Here we develop a strategy for siRNA nanoninjection of the human corneal endothelium. We show that nanoneedles can deliver p16-targeting siRNA to primary human corneal endothelial cells in vitro without toxicity. The nanoinjection of siRNA induces p16 silencing and increases cell proliferation, as monitored by ki67 expression. Furthermore, siRNA nanoinjection targeting the human corneal endothelium is non-toxic ex vivo and silences p16 in transfected cells. These data indicate that nanoinjection can support targeted RNAi therapy for the treatment of endothelial corneal dysfunction.